Pharmacokinetic/Pharmacodynamic Modeling of Efficacy and Hypoglycemia Rate When Switching From Once-Daily Basal Insulin to Once-Weekly Insulin Icodec Without or With a One-Time Additional Dose in Insulin-Experienced Individuals With Type 2 Diabetes.

Objective: Insulin icodec (icodec), a once-weekly basal insulin analog, has been investigated in the phase 3a ONWARDS clinical trial program. This pharmacokinetic (PK)/pharmacodynamic (PD) modeling analysis of data from the ONWARDS 2 and 4 trials investigated efficacy outcomes and hypoglycemia rate in insulin-experienced individuals with type 2 diabetes when switching from daily basal insulin to icodec without or with a 50% one-time additional dose for the first injection only.
Methods: Data from 2 randomized, 26-week, phase 3a trials of insulin-experienced individuals with type 2 diabetes on a basal (ONWARDS 2) or basal-bolus (ONWARDS 4) insulin regimen were used for PK/PD model development and validation. The effect of switching to icodec without versus with a 50% one-time additional dose on prebreakfast self-measured blood glucose, glycated hemoglobin, weekly insulin dose, and clinically significant hypoglycemia was assessed.
Results: Model predictions suggested that switching to icodec without versus with a 50% one-time additional dose would result in a mild, transient (1-2 weeks) increase in prebreakfast self-measured blood glucose after treatment initiation that would decrease to matching levels between groups by week 4 and remain similar between groups until end of treatment (week 26). There were no model-predicted differences between groups in glycated hemoglobin reduction or clinically significant hypoglycemia over the 26-week study period or in weekly icodec dose at week 26.
Conclusions: This PK/PD model analysis suggests that omitting administration of a 50% one-time additional dose when switching to icodec from daily basal insulin would not be predicted to result in any sustained effects.
Competing Interests: Disclosure I.L. has received research funding (paid to the institution they are affiliated with) from Boehringer Ingelheim, Merck, Mylan, Novo Nordisk, Pfizer, and Sanofi, and has received advisory/consulting fees and/or other support from AstraZeneca, Bayer, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, GI Dynamics, Intarcia Therapeutics, Intercept Pharmaceuticals, Johnson & Johnson, MannKind, Merck, Mylan, Novartis, Novo Nordisk, Pfizer, Sanofi, Shionogi, Structure Therapeutics, Target Pharma, Valeritas, and Zealand Pharma. B.Á., N.R.K., C.L., and F.K.K. are employees and shareholders of Novo Nordisk. A.V. has received fees for activities as an advisory board member for Abbott Diabetes Care, AstraZeneca, Eli Lilly, Medtronic, and Novo Nordisk; has carried out speaker activities for Abbott Diabetes Care, AstraZeneca, Eli Lilly, Medtronic, Novo Nordisk, and Roche; and has research grants from Anji Pharmaceuticals, Eli Lilly, and Novo Nordisk. I.L., A.V., and F.K.K. have received consultancy fees from Novo Nordisk. I.L. and A.V. have received grants from Novo Nordisk during the conduct of the ONWARDS 3 trial.
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